Psychological stress and functional ovarian suppression in women with PCOM: an observational study of FHA-like neuroendocrine phenotypes

Abstract

Propose: To examine how chronic psychological stress alters gonadotropin dynamics and disrupts ovarian endocrine function in women with polycystic ovarian morphology (PCOM), and to discuss the modulatory role of leptin in this process. Methods: In this cross-sectional study of 134 women, participants were classified into four groups: three subgroups of women with oligomenorrhea—PCOM with stress, PCOM without stress, and NON-PCOM/NON-STRESS—and a comparison group of eumenorrheic controls. Psychological stress was assessed with validated psychometric instruments (STAI, HADS, PSS-10), and a composite Stress Index was derived. PCOM was defined according to the 2023 International Evidence-based Guideline for PCOS. Stress status was classified using established cut-offs for each instrument, with non-stress cohorts defined by scores consistently below clinical thresholds. Hormonal profiling included LH, FSH, estradiol, AMH, leptin, cortisol, and ACTH. Mediation and moderation models were employed to examine the relationships among stress, leptin, the LH/FSH ratio, and ovarian endocrine markers, as AMH and estradiol. Results: Women in the PCOM–STRESS group exhibited significantly lower LH levels, LH/FSH ratios, and AMH concentrations compared to PCOM–NON–STRESS, despite similar ovarian morphology and preserved FSH levels. Mediation analysis revealed that the LH/FSH ratio significantly mediated the effect of psychological stress on both estradiol and AMH levels. Moderation analysis indicated that leptin modulated the impact of stress on the LH/FSH ratio (interaction p = 0.004), with more pronounced suppressive effects of psychological stress under low leptin levels. Despite high psychological stress, women in the PCOM–STRESS group showed no activation of the HPA axis, suggesting neuroendocrine resilience or adaptation. These findings highlight the clinical value of assessing both psychological and metabolic context in women with ambiguous ovulatory dysfunction. Conclusion: Chronic psychological stress in women with PCOM is associated with functional suppression of LH and ovarian endocrine output, reflecting an attenuation of the typical PCOS endocrine phenotype despite the polycystic ovarian morphology. Leptin modulates individual susceptibility to stress-induced reproductive suppression, acting as a potential permissive signal of hypothalamic resilience. Assessing gonadotropin ratios and metabolic context may improve diagnostic accuracy in women with ambiguous ovulatory dysfunction.